Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation
Abstract
:1. Introduction
2. Results
2.1. Erythrogram (Table 1)
Treatment | RBC (×106/μL) | HGB (g/dL) | HCT (%) | MCH (pg) | MCHC (g/dL) | MCV (fL) | RDW (%) |
---|---|---|---|---|---|---|---|
Filtered water, p.o. | 7.53 ± 0.28 | 11.90 ± 0.44 | 30.38 ± 1.02 | 15.83 ± 0.09 | 39.12 ± 0.41 | 40.40 ± 0.40 | 17.83 ± 0.41 # |
CP 25 mg/Kg, p.o. | 7.60 ± 0.12 # | 12.05 ± 0.26 | 30.57 ± 0.66 | 15.85 ± 0.16 | 39.45 ± 0.75 | 40.22 ± 0.46 | 16.80 ± 0.60 |
Cry 1Ac 6.75 mg/kg, p.o. | 8.07 ± 0.13 ○,# | 12.02 ± 0.18 | 30.23 ± 0.48 | 14.87 ± 0.10 **,○ | 39.77 ± 0.29 | 37.45 ± 0.27 **,○,# | 13.78 ± 0.19 **,○,# |
Cry 1Ac 13.5 mg/kg, p.o. | 8.30 ± 0.19 ○,# | 12.53 ± 0.25 | 31.12 ± 0.71 | 15.10 ± 0.11 **,○,# | 40.30 ± 0.29 | 37.50 ± 0.26 **,○,# | 13.57 ± 0.16 **,○,# |
Cry 1Ac 27 mg/kg, p.o. | 7.98 ± 0.12 ○ | 12.25 ± 0.24 | 30.42 ± 0.56 | 15.33 ± 0.20 | 40.28 ± 0.56 | 38.08 ± 0.22 **,○,# | 16.93 ± 0.36 ○,b |
p-values | 0.029 | 0.570 | 0.918 | 0.002 | 0.374 | 0.000 | 0.000 |
Filtered water, i.p. | 7.94 ± 0.14 | 12.32 ± 0.22 | 31.53 ± 0.63 | 15.35 ± 0.26 | 39.10 ± 0.31 | 39.25 ± 0.6 | 16.27 ± 0.44 |
CP 25 mg/Kg, i.p. | 8.12 ± 0.12 | 12.63 ± 0.24 | 31.22 ± 0.43 | 15.57 ± 0.17 | 40.48 ± 0.22 | 38.42 ± 0.28 | 16.63 ± 0.30 |
Cry 1Ac 6.75 mg/kg, i.p. | 7.32 ± 0.17 *,○ | 11.43 ± 0.19 | 30.13 ± 0.34 | 15.65 ± 0.37 | 37.93 ± 0.57 ○ | 41.30 ± 1.15 | 17.90 ± 0.44 *,○ |
Cry 1Ac 13.5 mg/kg, i.p. | 7.53 ± 0.13 ○ | 12.05 ± 0.27 | 30.57 ± 0.97 | 16.02 ± 0.16 | 39.52 ± 0.66 | 40.57 ± 0.67 | 17.90 ± 0.50 * |
Cry 1Ac 27 mg/kg, i.p. | 7.50 ± 0.50 | 11.87 ± 0.74 | 30.73 ± 1.70 | 15.87 ± 0.35 | 38.55 ± 0.69 | 41.15 ± 0.89 | 16.80 ± 0.61 |
p-values | 0.184 | 0.284 | 0.853 | 0.483 | 0.024 | 0.059 | 0.061 |
Total p-values | 0.005 | 0.435 | 0.972 | 0.007 | 0.017 | 0.000 | 0.000 |
2.2. Leukogram (Table 2)
Treatment | WBC (×103/μL) | Lymphocytes (×103/μL) | Neutrophils + Monocytes (×103/μL) | Eosinophils (×103/μL) |
---|---|---|---|---|
Filtered water, p.o. | 4.63 ± 0.74 | 3.35 ± 0.55 | 1.22 ± 0.20 | 0.07 ± 0.05 |
CP 25 mg/Kg, p.o. | 5.37 ± 0.77 | 3.73 ± 0.53 | 1.58 ± 0.34 # | 0.05 ± 0.03 |
Cry 1Ac 6.75 mg/kg, p.o. | 5.22 ± 0.56 | 4.05 ± 0.47 | 1.15 ± 0.12 # | 0.02 ± 0.02 # |
Cry 1Ac 13.5 mg/kg, p.o. | 5.07 ± 0.68 | 3.75 ± 0.48 | 1.23 ± 0.33 # | 0.08 ± 0.05 |
Cry 1Ac 27 mg/kg, p.o. | 6.90 ± 0.89 * | 4.25 ± 0.45 # | 2.52 ± 0.66 | 0.13 ± 0.10 |
p-values | 0.458 | 0.655 | 0.643 | 0.816 |
Filtered water, i.p. | 5.00 ± 1.33 | 3.83 ± 0.65 | 1.05 ± 0.89 | 0.12 ± 0.04 |
CP 25 mg/Kg, i.p. | 5.05 ± 0.49 | 4.83 ± 0.49 | 0.10 ± 0.00 | 0.12 ± 0.02 |
Cry 1Ac 6.75 mg/kg, i.p. | 6.82 ± 1.35 | 3.43 ± 0.57 | 3.20 ± 0.78 ○ | 0.18 ± 0.06 |
Cry 1Ac 13.5 mg/kg, i.p. | 5.58 ± 0.59 | 2.75 ± 0.31 ○ | 2.75 ± 0.42 ○ | 0.08 ± 0.03 |
Cry 1Ac 27 mg/kg, i.p. | 5.25 ± 0.86 | 2.47 ± 0.35 ○ | 2.58 ± 0.63 ○ | 0.20 ± 0.06 |
p-values | 0.686 | 0.018 | 0.002 | 0.541 |
Total p-values | 0.766 | 0.078 | 0.000 | 0.140 |
2.3. Plateletgram (Table 3)
Treatment | PLT (×103/μL) | MPV (fl) | P-LCR (%) | PDW (fl) |
---|---|---|---|---|
Filtered water, p.o. | 1219.00 ± 56.64 | 6.93 ± 0.10 # | 10.88 ± 0.81 # | 6.95 ± 0.11 |
CP 25 mg/Kg, p.o. | 978.67 ± 93.57 * | 7.10 ± 0.30 | 11.23 ± 2.33 | 7.25 ± 0.24 |
Cry 1Ac 6.75 mg/kg, p.o. | 1312.17 ± 83.67 ○ | 6.30 ± 0.08 **,○,# | 7.33 ± 0.60 **,○ | 6.57 ± 0.02 *,○,# |
Cry 1Ac 13.5 mg/kg, p.o. | 1338.00 ± 57.97 ○ | 6.30 ± 0.12 *,○,# | 7.62 ± 0.78 *,# | 6.55 ± 0.04 *,○,a,# |
Cry 1Ac 27 mg/kg, p.o. | 1224.67 ± 58.93 ○ | 6.90 ± 0.09 ○ | 9.63 ± 0.88 | 7.03 ± 0.10 b,# |
p-values | 0.029 | 0.001 | 0.024 | 0.002 |
Filtered water, i.p. | 1137.50 ± 95.72 | 6.58 ± 0.05 | 7.08 ± 0.65 | 7.00 ± 0.10 |
CP 25 mg/Kg, i.p. | 1133.00 ± 69.15 | 6.90 ± 0.09 * | 9.67 ± 0.48 * | 7.05 ± 0.11 |
Cry 1Ac 6.75 mg/kg, i.p. | 1181.05 ± 67.69 | 7.05 ± 0.12 * | 8.68 ± 0.78 | 7.42 ± 0.11 *,○ |
Cry 1Ac 13.5 mg/kg, i.p. | 1225.00 ± 74.21 | 7.30 ± 0.14 ** | 10.67 ± 1.18 * | 7.62 ± 0.11 **,○ |
Cry 1Ac 27 mg/kg, i.p. | 1000.33 ± 90.73 | 7.27 ± 0.14 ** | 11.23 ± 0.89 * | 7.57 ± 0.08 **,○ |
p-values | 0.378 | 0.004 | 0.015 | 0.000 |
Total p-values | 0.066 | 0.000 | 0.004 | 0.000 |
2.4. Micronucleus (MN) Test (Table 4)
Treatment | MN-NCE | Polychromatic Erythrocytes (PCE) | |
---|---|---|---|
MN-PCE | Cellular Proliferation Index (%PCE) | ||
Filtered water, p.o. | 2.00 ± 1.44 | 2.50 ± 1.43 | 52.61 ± 1.01 # |
CP 25 mg/Kg, p.o. | 2.17 ± 0.48 # | 3.50 ± 0.62 # | 45.97 ± 1.21 *,# |
Cry 1Ac 6.75 mg/kg, p.o. | 0.83 ± 0.31 ○,# | 2.33 ± 0.67 # | 53.08 ± 1.54 ○ |
Cry 1Ac 13.5 mg/kg, p.o. | 0.83 ± 0.31 ○,# | 2.00 ± 0.37 # | 52.38 ± 0.80 ○ |
Cry 1Ac 27 mg/kg, p.o. | 1.33 ± 0.21 | 3.33 ± 0.76 # | 49.49 ± 2.14 |
p-values | 0.179 | 0.307 | 0.007 |
Filtered water, i.p. | 0.17 ± 0.17 | 2.33 ± 0.42 | 70.13 ± 0.87 |
CP 25 mg/Kg, i.p. | 14.33 ± 1.99 ** | 26.83 ± 2.52 ** | 66.56 ± 1.30 |
Cry 1Ac 6.75 mg/kg, i.p. | 4.17 ± 0.48 **,○ | 7.67 ± 1.23 **,○ | 47.99 ± 1.20 **,○ |
Cry 1Ac 13.5 mg/kg, i.p. | 4.67 ± 1.15 **,○ | 6.00 ± 0.37 **,○ | 51.72 ± 0.95 **,○ |
Cry 1Ac 27 mg/kg, i.p. | 2.50 ± 0.56 **,○ | 5.67 ± 0.56 **,○ | 51.36 ± 1.52 **,○ |
p-values | 0.000 | 0.000 | 0.000 |
Total p-values | 0.000 | 0.000 | 0.000 |
3. Discussion
4. Experimental Section
4.1. Chemicals
4.2. Bt Cry1Ac Spore-Crystals
4.3. Animals and Experimental Design
4.4. Statistical Analysis
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Mezzomo, B.P.; Miranda-Vilela, A.L.; Grisolia, C.K. Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation. Toxins 2015, 7, 5348-5358. https://doi.org/10.3390/toxins7124881
Mezzomo BP, Miranda-Vilela AL, Grisolia CK. Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation. Toxins. 2015; 7(12):5348-5358. https://doi.org/10.3390/toxins7124881
Chicago/Turabian StyleMezzomo, Bélin Poletto, Ana Luisa Miranda-Vilela, and Cesar Koppe Grisolia. 2015. "Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation" Toxins 7, no. 12: 5348-5358. https://doi.org/10.3390/toxins7124881
APA StyleMezzomo, B. P., Miranda-Vilela, A. L., & Grisolia, C. K. (2015). Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation. Toxins, 7(12), 5348-5358. https://doi.org/10.3390/toxins7124881